The aim of this proposal is to organize a scientific conference entitled "Proteases, Microenvironment and Cancer" to be held at Coconut Point, Florida from November 30-December 3, 2005. This AACR conference is a sequel to the highly successful meetings held in March, 1996; June, 1998; and October, 2002. The first two of these conferences were traditionally focused on the three major families of matrix degrading proteases involved in tumor invasion and metastasis, the matrix metalloproteinases (MMPs), the serine proteinases (plasminogen-plasminogen activator system) and the cysteine proteinases and cathepsins. These two meetings, organized by Drs. Lynn Matrisian and Bonnie Sloane, were very successful, with more than two hundred participants. A third meeting was then organized by Drs. Ruth Muschel and Yves De Clerck in 2002 at Hilton Head, South Carolina, with a broader focus on the ECM and the examination of the more complex function of matrix degrading proteases. This meeting included sessions on integrin and integrin signaling, function of the proteolyzed ECM in cell proliferation and apoptosis, protease receptorintegrin cross talk, cell migration, metastasis and angiogenesis, and imaging technologies. It was also a very successful meeting attended by more than 250 participants. This upcoming meeting will focus on the tumor microenvironment at large and will include, in addition to more traditional sessions on proteases, angiogenesis, metastasis and the ECM, sessions covering critical aspects of the microenvironment such as bone invasion, inflammation, tumor cell-stromal cell interaction, hypoxia and stress in cancer progression, and tumor cell plasticity.